|Year : 1991 | Volume
| Issue : 4 | Page : 174-175
Anti-insulin antibodies and retinopathy in juvenile onset type-1 diabetes
K Sharma, PK Khosla, HK Tiwari, RK Sharma, JS Bajaj
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Department of Medicine, Department of Anatomy, All Institute of Medical Sciences, New Delhi, India
Department of Neuro-Ophthalmology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Post Box 375, Lucknow - 226001
Source of Support: None, Conflict of Interest: None
Juvenile diabetics have severe loss of beta cell function and require replacement therapy with insulin. Insulin antigenicity can produce anti-insulin antibodies resulting in allergic reactions and insulin resistance. The role of insulin-anti-insulin antibody complexes in the development and progress of chronic diabetic complications like microangiopathy is not very clear. In the present study, there was statistically a significant trend of higher insulin antibody binding levels in IDDM patients who developed retinopathy. Though there was a trend of higher insulin antibody in IDDM patients with retinopathy, there was no association between insulin antibody and HLA antigen which some authors have reported.
|How to cite this article:|
Sharma K, Khosla P K, Tiwari H K, Sharma R K, Bajaj J S. Anti-insulin antibodies and retinopathy in juvenile onset type-1 diabetes. Indian J Ophthalmol 1991;39:174-5
|How to cite this URL:|
Sharma K, Khosla P K, Tiwari H K, Sharma R K, Bajaj J S. Anti-insulin antibodies and retinopathy in juvenile onset type-1 diabetes. Indian J Ophthalmol [serial online] 1991 [cited 2021 Aug 4];39:174-5. Available from: https://www.ijo.in/text.asp?1991/39/4/174/24429
| Introduction|| |
Juvenile diabetics have severe loss of beta cell function and require replacement therapy with insulin. Insulin antigenicity can produce anti-insulin antibodies resulting in allergic reactions  and insulin resistance  The role of insulin-anti-insulin antibody complexes in the development and progress of chronic diabetic complications like microangiopathy is not very clear. The present study investigates the relationship between anti-insulin antibody and retinopathy in insulin dependent diabetes mellitus (IDDM).
| Material and methods|| |
Thirty five patients of IDDM were studied for the presence of diabetic retinopathy by fluorescein angiography. They were divided into various groups depending on the severity of retinopathy : Group I-no retinopathy (20 patients); Group II with retinopathy (15 patients) further subdivided into Ila - mild retinopathy (6 patients) and Ilb - severe retinopathy (proliferative and maculopathy, 9 patients).
Patients showing loss of beta cell function indicated by low serum C peptide immunoreactivity (RIA kit,Novo Research Institute, Denmark) and low serum immunoreactive insulin ; both baseline and after glucose load, were included in the study.
Serum insulin antibody: Fasting blood samples were analysed for insulin antibody by radioimmunoassay (RIA) . Percentage of insulin binding was determined by a RIA procedure usin dextran coated charcoal method and titration with 125 insulin (monocomponent porcine insulin; Novo Research Institute, Immunochemical Laboratory, Denmark). Percentage of insulin antibody binding was estimated in undiluted serum and after dilutions i.e. 1:10, 1:50 and 1:100.
The patients also underwent HLA typing for A,B,C loci by two stage microlymphocytotoxicity method of Terasaki and McClelland .
| Observation|| |
Insulin antibody binding: The binding of 125 labelled pork insulin by the serum sample in IDDM (35 patients), were expressed as percent of labelled insulin bound [Figure - 1]. Sixty percent of patients with retinopathy and only 20% without retinopathy had moderate or high serum insulin binding levels. This difference was statistically significant ([Table - 1]. P>0.05). Mean values of percentage of insulin antibody binding in retinopathy group was also higher than the no-retinopathy group [Table - 2], but this failed to reach statistical significance.
HLA and anti-insulin antibodies: There was no significant association between any HLA antigen and insulin binding [Table - 3].
| Discussion|| |
Some workers have suggested that immune complexes may play a role in the degenerative diseases of diabetes including microangiopathy . The antigen antibody complexes in the plasma of diabetics are partially due to insulin and its antibodies . Cytotoxic immune complexes could be formed as a combination of high affinity insulin antibody with previously se-questered insulin in the vascular wall.
In the present study, there was statistically a significant trend of higher insulin antibody binding levels in IDDM patients who developed retinopathy [Table - 1]. Anderson  has also found that the frequency of high insulin antibody titre was significantly greater among diabetics with complications like retinopathy and insulin-antinsulin antibody complexes may be involved in aggravating the microvascular pathology. Other workers have failed to find such a relationship 
Evidence is slim but increasing to support that diabetic microangiopathy may be caused or accelerated by immune complexes. Atkins et al  have found strong correlation between the insulin antibody and islet cell antibody and presence of both increased the likelihood of autoimmune phenomenon.
HLA and insulin antibody: The susceptibility to retinopathy in IDDM has been correlated with particular HLA antigens . The possibility that this could be mediated by production of insulin antibodies has been investigated. In our present study, though there was a trend of higher insulin antibody in IDDM patients with retinopathy, there was no association between insulin antibody and HLA antigen [Table - 3]. Some workers  have found such an association with HLA 15 but others have failed to confirm it  In conclusion, the higher levels of anti-insulin antibody seen in patients of IDDM with retinopathy did not show any association with HLA. It remains speculative whether raised levels of anti-insulin antibody have a role to play in either initiation or aggravation of retinopathy or alternatively they may simply be a reflection of non specific secondary tissue damage
| Summary|| |
Thirty five patients of insulin dependent diabetes mellitus (IDDM) were investigated for retinopathy by fluorescein angiography. Serum levels of insulin antibody binding were correlated with the retinopathy. Patients with retinopathy had a trend towards higher serum insulin antibody binding levels which was statistically significant. There was no association between HLA phenotypes and the insulin antibody levels.
| References|| |
Kumar, D.. 1977, J. Clin. Endocrinol. Metab, 45:1159.
Andersen, O.O., 1975, Acta Endocrinol. 78:723.
Leslie, R.D.G., Barnett, A.H., Pyke, D.A., 1979. Lancet, 1;997.
Khardori, R., Bajaj. J.S., Deo, M.G., Bansal, D.O., 1980, J. Endocrine Invest., 3:273.
Bersen, S.A., Yalow, R.S., 1962, Immunoassay of hormones. Ciba Foundation on Endocrinology.. Vol.14, Churchill. London.
Terasaki, PI., McClellamd, J.D., 1964, Nature, 204:998.
Berns. A. W., Owens, C T., Hirata, Y., Blumenthal. H.T., 1962, Diabetes. 11:308.
DiMario. U., lavicoli, M., Andereani, U., 1980 Diabetologica, 19:89.
Andersen. O.O.. 1976, Acta Endrocrinol.. 83:329.
Gray. R.S., Starkey, I.R., Rainbow, S., Kurtz, A.B., Abdel Khalik, A..Urabanik, S.. Elton. R.A.. Duncan, L.J.P. Clarke, B.F., 1982 Br. J. Ophthalmol., 66:280.
Atlins, M.A.. Maclarem, N.K., Riley, W.J., Winter, W.E., Fisk, D.D., Spillar, R.P. 1986, Diabetes. 35:894.
Barbosa. J., Ramsay, R. C., Knobloch, W.C., 1980, Am. J. Ophthalmol.90:148.
Bodansky, H.J., Wolf, E., Cudworth. A.G., Dean B.M., Nineham, L.J., Bottazzo, G.F, Mathews, J.A., Kurtz, A.B., Kohner, E.M. 1982, Diabetes, 31:70.
[Figure - 1]
[Table - 1], [Table - 2], [Table - 3]
|This article has been cited by|
||Molecular mechanisms of insulin resistance and associated diseases
| ||Mlinar, B., Marc, J., Jane, A., Pfeifer, M. |
| ||Clinica Chimica Acta. 2007; 375(1-2): 20-35 |
||Reduced antioxidant potential & sensitivity to oxidation in plasma low density lipoprotein fraction in type 2 diabetes mellitus patients
| ||Ergüder, I.B., Karagenç, N., Karaca, L. |
| ||Indian Journal of Medical Research. 2006; 124(2): 207-210 |
||Molecular mechanism of insulin resistance, obesity and metabolic syndrome | [Molekularni mechanizmi inzulinske rezistencije, pretilosti i metaboličkog sindroma]
| ||Mlinar, B., Marc, J., Pfeifer, M. |
| ||Biochemia Medica. 2006; 16(1): 8-24 |
||Immune response to enzyme replacement therapy: Clinical signs of hypersensitivity reactions and altered enzyme distribution in a high titre rat model
| ||Brooks, D.A., Hopwood, J.J., King, B.M. |
| ||Biochimica et Biophysica Acta - Molecular Basis of Disease. 1998; 1407(2): 163-172 |